Protein-Functionalized Nanoparticles Derived from End-Functional Polymers and Polymer Prodrugs for Crossing the Blood-Brain Barrier.

Protein-Functionalized Nanoparticles Derived from End-Functional Polymers and Polymer Prodrugs for Crossing the Blood-Brain Barrier. Eur J Pharm Biopharm. 2019 Jun 06;: Authors: Cox A, Vinciguerra D, Re F, Dal Magro R, Mura S, Masserini M, Couvreur P, Nicolas J Abstract Nanoparticles may provide a viable way for neuroprotective drugs to cross the blood-brain barrier (BBB), which limits the passage of most drugs from the peripheral circulation to the brain. Heterotelechelic polymer prodrugs comprising a neuroprotective model drug (adenosine) and a maleimide functionality were synthesized by the "drug-initiated" approach and subsequent nitroxide exchange reaction. Nanoparticles were obtained by nanoprecipitation and exhibited high colloidal stability with diameters in the 162-185 nm range and narrow size distributions. Nanoparticles were then covalently surface-conjugated to different proteins (albumin, α2-macroglobulin and fetuin A) to test their capability of enhancing BBB translocation. Their performances in terms of endothelial permeability and cellular uptake in an in vitro BBB model were compared to that of similar nanoparticles with surface-adsorbed proteins, functionalized or not with the drug. It was shown that bare NPs (i.e., NPs not surface-functionalized with proteins) without the drug exhibited significant permeability and cellular uptake, which were further enhanced by NP surface functionalization with α2-macroglobulin....
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Biopharm Source Type: research